STAT5B, Akt and p38 Signaling Activate <i>FTZ-F1</i> to Regulate the Xenobiotic Tolerance-Related Gene <i>SlCyp9a75b</i> in <i>Spodoptera litura</i>

Cytochrome P450 monooxygenases in insects have been verified to implicated in insecticide and phytochemical detoxification metabolism. However, the regulation of P450s, which are modulated by signal-regulated transcription factors (TFs), is less well studied in insects. Here, we found that the Malpighian tubule specific P450 gene <i>SlCYP9A75b</i> in <i>Spodoptera litura</i> is induced by xenobiotics. The transgenic <i>Drosophila</i> bioassay and RNAi results indicated that this P450 gene contributes to α-cypermethrin, cyantraniliprole, and nicotine tolerance. In addition, functional analysis revealed that the MAPKs p38, PI3K/Akt, and JAK-STAT activate the transcription factor fushi tarazu factor 1 (<i>FTZ-F1</i>) to regulate <i>CYP9A75b</i> expression. These findings provide mechanistic insights into the contributions of CYP9A genes to xenobiotic detoxification and support the possible involvement of different signaling pathways and TFs in tolerance to xenobiotics in insects.